6rt5: Difference between revisions
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The | ==The YTH domain of YTHDC1 protein in complex with Gm6AC oligonucleotide== | ||
<StructureSection load='6rt5' size='340' side='right'caption='[[6rt5]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6rt5]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RT5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RT5 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=6MZ:N6-METHYLADENOSINE-5-MONOPHOSPHATE'>6MZ</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6rt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rt5 OCA], [http://pdbe.org/6rt5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rt5 RCSB], [http://www.ebi.ac.uk/pdbsum/6rt5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rt5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/YTDC1_HUMAN YTDC1_HUMAN]] RNA-binding protein that regulates alternative splice site selection.<ref>PMID:20167602</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
N6-methyladenosine (m(6)A) is the most prevalent chemical modification in human mRNAs. Its recognition by reader proteins enables many cellular functions, including splicing and translation of mRNAs. However, the binding mechanisms of m(6)A-containing RNAs to their readers are still elusive due to the unclear roles of m(6)A-flanking ribonucleotides. Here, we use a model system, YTHDC1 with its RNA motif 5'-G-2G-1(m(6)A)C+1U+2-3', to investigate the binding mechanisms by atomistic simulations, X-ray crystallography, and isothermal titration calorimetry. The experimental data and simulation results show that m(6)A is captured by an aromatic cage of YTHDC1 and the 3' terminus nucleotides are stabilized by cation-pi-pi interactions, while the 5' terminus remains flexible. Moreover, simulations of unbound RNA motifs reveal that the methyl group of m(6)A and the 5' terminus shift the conformational preferences of the oligoribonucleotides to the bound-like conformation, thereby facilitating the association process. The binding mechanisms may help in the discovery of chemical probes against m(6)A reader proteins. | |||
Flexible binding of m(6)A reader protein YTHDC1 to its preferred RNA motif.,Li Y, Bedi RK, Wiedmer L, Huang D, Sledz P, Caflisch A J Chem Theory Comput. 2019 Oct 31. doi: 10.1021/acs.jctc.9b00987. PMID:31670957<ref>PMID:31670957</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6rt5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Bedi, R]] | [[Category: Bedi, R]] | ||
[[Category: Caflisch, A]] | |||
[[Category: Sledz, P]] | [[Category: Sledz, P]] | ||
[[Category: | [[Category: Epitranscriptomic]] | ||
[[Category: Protein-rna interaction]] | |||
[[Category: Rna binding protein]] | |||
Revision as of 09:57, 27 November 2019
The YTH domain of YTHDC1 protein in complex with Gm6AC oligonucleotideThe YTH domain of YTHDC1 protein in complex with Gm6AC oligonucleotide
Structural highlights
Function[YTDC1_HUMAN] RNA-binding protein that regulates alternative splice site selection.[1] Publication Abstract from PubMedN6-methyladenosine (m(6)A) is the most prevalent chemical modification in human mRNAs. Its recognition by reader proteins enables many cellular functions, including splicing and translation of mRNAs. However, the binding mechanisms of m(6)A-containing RNAs to their readers are still elusive due to the unclear roles of m(6)A-flanking ribonucleotides. Here, we use a model system, YTHDC1 with its RNA motif 5'-G-2G-1(m(6)A)C+1U+2-3', to investigate the binding mechanisms by atomistic simulations, X-ray crystallography, and isothermal titration calorimetry. The experimental data and simulation results show that m(6)A is captured by an aromatic cage of YTHDC1 and the 3' terminus nucleotides are stabilized by cation-pi-pi interactions, while the 5' terminus remains flexible. Moreover, simulations of unbound RNA motifs reveal that the methyl group of m(6)A and the 5' terminus shift the conformational preferences of the oligoribonucleotides to the bound-like conformation, thereby facilitating the association process. The binding mechanisms may help in the discovery of chemical probes against m(6)A reader proteins. Flexible binding of m(6)A reader protein YTHDC1 to its preferred RNA motif.,Li Y, Bedi RK, Wiedmer L, Huang D, Sledz P, Caflisch A J Chem Theory Comput. 2019 Oct 31. doi: 10.1021/acs.jctc.9b00987. PMID:31670957[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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